Immunology and Infectious Disease Commons^™

Porphyromonas Gingivalis Inactivates Anti-Viral Immunity At The Oral And Respiratory Epithelium., Carlos J. Rodriguez Hernandez

Electronic Theses and Dissertations

The host microbiome plays an important role in fine-tuning host immune responses in a manner that ultimately impacts outcomes in viral infection. Symbiotic relationships between commensal bacteria and host epithelial and immune cells prime interferon (IFN) signaling, modulating the nature and intensity of the immune response to viral infections at mucosal barrier surfaces. In this doctoral thesis, I explore how dysbiotic shifts in the oral microbial communities modulate antiviral responses at the oral and oro-respiratory mucosal barriers. I identified that in response to a viral challenge, gingival epithelial cells (GECs) preferentially induced type III IFNs (IFN-λ), a newly described family …

Inhibition Of Pro-Inflammatory Lipid Mediators By Yersinia Pestis., Amanda Brady

Electronic Theses and Dissertations

Yersinia pestis causes the human disease known as plague. A key manifestation of plague is a delayed inflammatory response. Because this delay in inflammation is required for virulence, I was interested in defining the molecular mechanisms used by Y. pestis to evade immune recognition. Eicosanoids are produced early during infection and necessary to initiate a rapid inflammatory response. Despite the importance of these lipids in mediating inflammation, the role of eicosanoids during plague has not been previously investigated. Using an intranasal mouse model infection, I determined the kinetics of eicosanoid synthesis during pneumonic plague. I further demonstrated that LTB_{4 …}

Regulation Of Cd4 T Cell Functions By Ncrna-Mediated Signaling Pathways During Chronic Viral Infections, Lam Nguyen

Electronic Theses and Dissertations

CD4 T cell homeostasis and competency are critical for the effectiveness of antiviral immunity. However, CD4 T cells derived from people living with HIV (PLWH) and individuals with chronic HCV infection often exhibit an inflammaging phenotype, evidenced by persistent inflammation, immune activation, exhaustion, senescence, and cellular apoptosis. Despite intensive investigations, the molecular mechanisms underlying CD4 T cell dysfunction in antiretroviral therapy (ART)-controlled PLWH and HCV-infected patients remain poorly understood. By investigating the roles of non-coding (nc)RNA transcripts in regulating the functions of CD4 T cells derived from PLWH and HCV-infected patients, we demonstrated that long non-coding (lnc)RNA - growth arrest-specific …

Antimicrobial Activity Of Cat Flea (Ctenocephalides Felis) Gut Proteins On Different Days After Blood Feeding, Dhruva K. Karnik

Honors College Theses

Cat fleas (Ctenocephalides felis) are a blood-feeding ectoparasitic insect and a common domestic pest found throughout the world. Because of their reliance on host blood, fleas are exposed to blood-borne pathogens; however, the flea gut lumen is a hostile environment for microbial colonization. For example, the gut epithelia differentially express immune genes in response to feeding. In the present study, we measured the antimicrobial activity of gut proteins from cat fleas at different days after feeding (2, 5, 7, and 14). Dissected flea guts were homogenized, passed through a syringe filter, and measured in a protein assay kit. …

Large-Scale Phenotyping Of Patients With Long Covid Post-Hospitalization Reveals Mechanistic Subtypes Of Disease, Felicity Liew, Claudia Efstathiou, Sara Fontanella, Matthew Richardson, Ruth Saunders, Dawid Swieboda, Jasmin K Sidhu, Stephanie Ascough, Shona C Moore, Noura Mohamed, Jose Nunag, Clara King, Olivia C Leavy, Omer Elneima, Hamish J C Mcauley, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Victoria C Harris, Linzy Houchen-Wolloff, Neil J Greening, Nazir I Lone, Matthew Thorpe, A A Roger Thompson, Sarah L Rowland-Jones, Annemarie B Docherty, James D Chalmers, Ling-Pei Ho, Alexander Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke S Howard, Daniel G Wootton, Jennifer K Quint, Thushan I De Silva, Antonia Ho, Christopher Chiu, Ewen M Harrison, William Greenhalf, J Kenneth Baillie, Malcolm G Semple, Lance Turtle, Rachael A Evans, Louise V Wain, Christopher Brightling, Ryan S Thwaites, Peter J M Openshaw, Phosp-Covid Collaborative Group, Isaric Investigators

Faculty, Staff and Student Publications

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers …

Role Of Toll-Like Receptor 2 In Macrophage Recognition And Response To Borrelia Burgdorferi, Yukiye A. Koide

Master's Theses

Lyme disease is the most common vector-borne disease in the US and will experience an uptick as the insect host, the ixodid tick, gains habitat with climate change. The causative agent of Lyme disease, Borrelia burgdorferi, is recognized by Toll-like receptor 2 (TLR2), which initiates the innate immune response. Here, I used ELISA and SEAP detection assays to determine that knocking out TLR2 in THP-1 macrophages reduces the amount of NFkB activation, as well as IL-10 and IL-1β secretion. Then, I used fluorescence microscopy and Incucyte assays to quantify the amount of phagocytosis performed by wild-type and knock-out THP-1 cells. …

Alteration Of The Interferon Alpha Signaling Pathway Significantly Affects Alzheimer's Disease Pathology In App/Ps1 Mouse Model., Ranjit Kumar Das, Nirakar Sahoo, Chun Xu, Hansapani Rodrigo, Michael Paul Murphy, Upal Roy, Deepa Roy

Research Symposium

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment, memory loss, and disturbances in behavior. The exact cause of the disease is unknown but there is evidence of molecular pathways alteration within the brain. Many molecular mechanisms have been studied for the progression of AD. Nonetheless, the contribution of the signal transducer and activator of transcription 1 (STAT1) and interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) genes have not been well established in AD pathology. This study aimed to investigate the contribution of STAT1 and IFIT3 in the BALB/C and APP/PS1 mouse models. We analyzed the STAT1 …

Staphylococcus Aureus Oleate Hydratase Produces Ligands That Activate Host Ppara, Christopher D. Radka, Matthew W. Frank, Tyler S. Simmons, Cydney N. Johnson, Jason W. Rosch, Charles O. Rock

Markey Cancer Center Faculty Publications

Commensal gut bacteria use oleate hydratase to release a spectrum of hydroxylated fatty acids using host-derived unsaturated fatty acids. These compounds are thought to attenuate the immune response, but the underlying signaling mechanism(s) remain to be established. The pathogen Staphylococcus aureus also expresses an oleate hydratase and 10- hydroxyoctadecanoic acid (h18:0) is the most abundant oleate hydratase metabolite found at Staphylococcal skin infection sites. Here, we show h18:0 stimulates the transcription of a set of lipid metabolism genes associated with the activation of peroxisome proliferator activated receptor (PPAR) in the RAW 264.7 macrophage cell line and mouse primary bone marrow-derived …

Transcriptional Induction Of Immune Pathway Genes And Subsequent Antibacterial Activity In The Digestive Tract Of The Cat Flea (Ctenocephalides Felis)., Katie A. Weber

College of Graduate Studies: Theses & Dissertations

Fleas (Order Siphonaptera) are ectoparasites that serve as vectors of several human diseases (cat scratch disease, flea-borne spotted fever, murine typhus, and plague). Typically, these pathogens are acquired through the ingestion of a host-derived bloodmeal; thus, the lumen of the gut is the first barrier encountered by imbibed pathogens. During the early stages of infection, microbes come into contact with surrounding midgut epithelial cells which trigger a series of host responses to combat local infection. Specifically, pathogen recognition leads to intracellular signaling and an increase in the production of antimicrobial peptides (AMPs) via the IMD and Toll immune pathways. While …

Corals In Crisis: A Transcriptomic Investigation Of Stony Coral Tissue Loss Disease, Kelsey M. Beavers

Biology Dissertations - Archive

Coral reefs face existential threats due to climate change and human activities. The combined effects of ocean warming, overfishing, pollution, and habitat destruction have fundamentally altered the functionality of coral reefs and are driving a drastic increase in the prevalence and severity of coral disease outbreaks. Stony coral tissue loss disease (SCTLD) has emerged one of the most devastating disturbances to Caribbean reef ecosystems on record. Despite notable progress, the cellular mechanisms driving SCTLD pathogenesis remain poorly understood. To address this issue, my dissertation investigates the gene expression, histopathology, immune protein activity, and symbiont community dynamics involved in SCTLD progression …

How Individuals’ Opinions Influence Society’S Resistance To Epidemics: An Agent-Based Model Approach, Geonsik Yu, Michael J. Garee, Mario Ventresca, Yuehwern Yih

Faculty Publications

Background: Protecting public health from infectious diseases often relies on the cooperation of citizens, especially when self-care interventions are the only viable tools for disease mitigation. Accordingly, social aspects related to public opinion have been studied in the context of the recent COVID-19 pandemic. However, a comprehensive understanding of the effects of opinion-related factors on disease spread still requires further exploration. Methods: We propose an agent-based simulation framework incorporating opinion dynamics within an epidemic model based on the assumption that mass media channels play a leading role in opinion dynamics. The model simulates how opinions about preventive interventions change over …

Migration-Associated Variation In Blood Parasitism, Body Condition, And Stress In Gambel’S White-Crowned Sparrows (Zonotrichia Leucophrys Gambelii), Julianna Deibel

Scripps Senior Theses

Migration is a widespread behavior in animals which both causes and is motivated by fluctuations in nutrient availability. Migration is ecologically important, as it connects areas of differing primary productivities and carries pathogens over distance. The relationship between migration and disease is complex, sensitive to anthropogenic disturbance, and influenced by ecological cycles as well as host, vector and parasite life cycles. Four central migration-infection mechanisms have been proposed: migratory susceptibility, migratory exposure, migratory escape, and migratory culling. These mechanisms may yield increased or decreased infection post-migration, based on migration’s physiological tax and the concentration of pathogens along migratory pathways.

To …

Endogenous Glucocorticoid Signaling Is Required For Normal Macrophage Response To H. Pylori Infection, Stuti Khadka

Graduate Theses, Dissertations, and Problem Reports (ETD)

Gastric cancer is the fifth leading cause of cancer-related deaths worldwide, affecting millions of people. H. pylori is the strongest risk factor for gastric cancer, with about 90% of the cases strongly associated with H. pylori infection. Half of the world's population is infected with this bacterium. However, only a small subset of the infected population (1-3 %) go on to develop gastric cancer. Diagnosis of the disease at an early stage is the biggest challenge because of the widespread prevalence of H. pylori infection and a long asymptomatic phase before the advanced stages. Patients are left with limited treatment …

Sars-Cov-2 Immunogenicity Models Inform Novel Strategies That Can Improve Mrna Vaccines, Katherine S. Lee

Graduate Theses, Dissertations, and Problem Reports (ETD)

The onset of the 2020 COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, issued a call to action in the fields of biomedical science and public health to implement strategies to contain and protect against the viral threat. In record times, pharmaceutical companies produced antiviral therapies and novel mRNA vaccines that were approved by the FDA for human use. With time, these vaccines were able to assist in ending the pandemic. However, time also showed the limits of mRNA vaccine induced immunity. Despite antibody responses being initially robust, titers dramatically wane with time and are limited in cross-neutralizing ability. As …

Cd8+ T Cell Metabolic Flexibility Elicited By Cd28-Ars2 Axis- Driven Alternative Splicing Of Pkm Supports Antitumor Immunity, G. Aaron Holling, Colin A. Chavel, Anand P. Sharda, Mackenzie M. Lieberman, Caitlin M. James, Shivana M. Lightman, Jason H. Tong, Guanxi Qiao, Tiffany R. Emmons, Thejaswini Giridharan, Shengqi Hou, Andrew M. Intlekofer, Richard M. Higashi, Teresa W. M. Fan, Andrew N. Lane, Kevin H. Eng, Brahm H. Segal, Elizabeth A. Repasky, Kevin P. Lee, Scott H. Olejniczak

Markey Cancer Center Faculty Publications

Metabolic flexibility has emerged as a critical determinant of CD8+ T-cell antitumor activity, yet the mechanisms driving the metabolic flexibility of T cells have not been determined. In this study, we investigated the influence of the nuclear cap-binding complex (CBC) adaptor protein ARS2 on mature T cells. In doing so, we discovered a novel signaling axis that endows activated CD8+ T cells with flexibility of glucose catabolism. ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events. Among these effects, the CD28-ARS2 axis suppressed the expression of the …

The Sewage Microbiome Dynamics Of Different Serving Neighborhoods In Charleston, Illinois, Sandra Chiamaka Okoye

Masters Theses

The complex microbial ecosystem within sewage systems holds significant implications for environmental and public health. Unlike studies on wastewater treatment plant microbiomes, upstream sewage systems have not been studied widely. This research investigated the dynamic sewage microbiome across diverse serving neighborhoods in Charleston, Illinois, encompassing residential, hospital, industrial, and university areas. Drawing upon recent advancements in microbiome research, the study aimed to unravel the spatial and temporal variations in microbial structures. Three times between June to December 2023 sewage samples were collected from manholes in the areas mentioned above. Community DNA was extracted and sequenced for the V4-V5 region of …

Evaluating The Role Of Glucocorticoids On The Host Response To Helicobacter Pylori Infection, Sara Druffner

Graduate Theses, Dissertations, and Problem Reports (ETD)

Gastric cancer is the fifth most common cancer and the fifth leading cause of cancer deaths worldwide. Helicobacter pylori infection is the number one risk factor for gastric cancer development. Roughly 50% of the world’s population is infected with H. pylori, though only 1-3% of those infected will develop cancer. H. pylori drives chronic inflammation that creates the requisite environment for carcinogenesis, yet it remains unclear why some individuals develop cancer and others do not. Most mechanistic studies are done in mice, however H. pylori is not a natural mouse pathogen. Research is typically done either with mouse-adapted strains of …

Role Of The Anti-Viral Immune Response In Neural Cell Modulation And Neurological Sequelae Of Childhood Viral Infections, Yashika Kamte

Electronic Theses and Dissertations

Viral infections of the central nervous system (CNS) often result in neurological sequelae and are considered a risk factor for the development of neurological disease. Moreover, the outcomes of a viral infection are largely dependent on the age of the host, with younger hosts developing more profound neuropathology. Perhaps the developing brain coupled with an immature immune system contributes to worse outcomes in the very young. Children suffering from brain infections are more prone to develop enduring neurological impairments even after recovery from the infection. Although majority of the brain growth occurs in utero, neurodevelopment continues throughout the juvenile …

Induction Of Protective Immunity In The Respiratory Tract With Ricin Toxin Immune Complexes, Lindsey Elizabeth Tolman

Legacy Theses & Dissertations (2009 - 2024)

Ricin toxin (RT) is generated in the seeds of Ricinus communis. The highly potent toxin is comprised of two subunits, RTA and RTB. RT enters cells using RTB before RTA separates itself and inactivates the ribosome, inducing cell stress, inflammation, and eventual death. RT is particularly damaging in the respiratory tract, where intoxication induces an inflammatory cytokine storm.Though there are currently no therapeutics for RT intoxication, our group has generated and characterized a wide variety of monoclonal antibodies (mAbs) against RT. Among the top candidates in our collection are the IgGs PB10 and SylH3. Previous studies have demonstrated their exceptional …

Characterizing The Regulation Of Candida Albicans Hyphal Morphogenesis In The Context Of Host Macrophages, Hannah Wilson

Dissertations and Theses (Open Access)

Candida albicans is a commensal fungus that resides on the skin, mucosal surfaces, and in the gut of an estimated 80% of individuals. Though generally harmless, C. albicans is capable of causing uncomfortable mucosal infections as well as deadly disseminated infections depending on the immune status of the host. Although antifungal therapeutics exist, the mortality rate associated with disseminated disease still lingers around 50%. Further, C. albicans is the fourth most common cause of all bloodstream infections and continues to present as a major clinical issue with less than satisfactory treatment options. For this reason, it is imperative to understand …

Intestinal Microbiome, Fecal Fermentation Profile, And Health Indices In Hiv Infected Men Versus Non-Infected Controls, Mary Andreae, Mary C. Andreae Mrs

Electronic Theses and Dissertations

Many HIV-positive (HIV+) males on Highly Active Anti-Retroviral Therapy (HAART) experience metabolic abnormalities, including Non-Alcoholic Fatty Liver Disease (NAFLD) and lipodystrophy. The intestinal microbiota and short chain fatty acids (SCFA), participate in bidirectional communication with their host. Dysbiosis in HIV+ males on HAART demonstrate a Prevotella-rich enterotype shaped by multiple factors including, medications, adiposity, diet, intestinal permeability, and lifestyle; our objective was to investigate these factors. 19 HIV+ and 21 HIV- males were enrolled. BMI and hip-to-waist ratio (H:W) were obtained, and FibroScan for liver health. Intestinal permeability markers Claudin-21, flagellin, and intestinal fatty acid binding protein (IFABP) in …

Sars-Cov-2: Tale Of A Microscopic Murderer, Josiah P. Garner

Quest

Independent Study

Research in progress for BIOL1406: Biology for Science Majors I

Faculty Mentor: Amina Tassa, Ph.D.

I am delighted to introduce Josiah Garner’s “SARS-CoV-2: Tale of a Microscopic Murderer.” This independent study assignment explores the impact of a novel, deadly, and worldwide virus. The assignment also examines the fast development of vaccines to control the spread and reduce the symptoms of the virus.

Josiah’s paper focuses on the early history of the emergence of COVID-19, the world response, and vaccine development. He demonstrates critical thinking skills and effectively utilizes various research methods to obtain and communicate his information. Josiah …

Antimicrobial Mitochondrial Reactive Oxygen Species Induction By Lung Epithelial Immunometabolic Modulation, Yongxing Wang, Vikram V Kulkarni, Jezreel Pantaleón García, Miguel M Leiva-Juárez, David L Goldblatt, Fahad Gulraiz, Lisandra Vila Ellis, Jichao Chen, Michael K Longmire, Sri Ramya Donepudi, Philip L Lorenzi, Hao Wang, Lee-Jun Wong, Michael J Tuvim, Scott E Evans

Faculty, Staff and Student Publications

Pneumonia is a worldwide threat, making discovery of novel means to combat lower respiratory tract infection an urgent need. Manipulating the lungs' intrinsic host defenses by therapeutic delivery of certain pathogen-associated molecular patterns protects mice against pneumonia in a reactive oxygen species (ROS)-dependent manner. Here we show that antimicrobial ROS are induced from lung epithelial cells by interactions of CpG oligodeoxynucleotides (ODN) with mitochondrial voltage-dependent anion channel 1 (VDAC1). The ODN-VDAC1 interaction alters cellular ATP/ADP/AMP localization, increases delivery of electrons to the electron transport chain (ETC), increases mitochondrial membrane potential (ΔΨm), differentially modulates ETC complex activities and consequently results in …

Molecular Mechanisms Behind Sars-Cov-2 Induced Host Genome Restructuring, Erin Simpson

Dissertations and Theses (Open Access)

Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2) has caused unprecedented morbidity and mortality worldwide. There are two pathophysiological hallmarks associated with severe patient outcomes after SARS-CoV-2 acute infection, namely delayed/weakened interferon production and overactive inflammatory responses. Our previous work has shown that these altered immune responses are due, at least in part, to significant alterations in 3D genome organization and epigenetic landscape following SARS-CoV-2 infection that are distinct from and more severe than changes caused by other viral infections or immune stimulants. While these changes at the chromatin level are important for understanding the immune dysregulation seen in some cases …

Investigating Host Cell Transcriptional Heterogeneity And Metabolism In Staphylococcus Aureus Biofilm Infections, Christopher M. Horn

Theses & Dissertations

Staphylococcus aureus (S. aureus) is a leading cause of prosthetic joint infection (PJI). These infections are often intractable due to biofilm formation, which are complex bacterial communities that adhere to biotic and abiotic surfaces. Within a biofilm, there is considerable heterogeneity in bacterial metabolism and gene expression that contributes to the establishment an anti-inflammatory milieu at the site of infection, which favors bacterial persistence even in the context of an immunocompetent host. This is due, in part, to the preferential recruitment of granulocytic myeloid-derived suppressor cells (G-MDSCs), which are a population of pathologically activated immature leukocytes that develop …

The Interface Between Host And Bacterial Metabolism During Staphylococcus Aureus Prosthetic Joint Infection, Blake P. Bertrand

Theses & Dissertations

Staphylococcus aureus (S. aureus) is a versatile pathogen that can occupy a wide range of niches within the human body, including implanted medical devices such as in prosthetic joint infection (PJI). S. aureus adheres to these medical devices and forms a biofilm, which is a community of bacteria contained within an extracellular matrix that leads to gradients in nutrient and oxygen availability. During PJI, the biofilm is recalcitrant to antibiotics and immune-mediated clearance, leading to treatment failure, mortality, and a high healthcare burden. This is partially due to skewing of the host immune system to an anti-inflammatory state, …

Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao

Graduate School of Biomedical Sciences Theses and Dissertations

Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …

Sex Differences In Host Resistance And Tolerance To The Common Avian Pathogen Mycoplasma Gallisepticum, Chloe Connelly

Biological Sciences Undergraduate Honors Theses

As we face the threat of global pandemics, one thing becomes clear: biological research is not just about the pursuit of the unknown, but about protecting our future. Understanding disease transmission and predicting pathogen epidemics is more important than ever. Prior studies have indicated that in populations where one sex engages in more social behaviors and movement that sex may drive disease transmission. This supports sex as a factor to consider in the study of epidemic dynamics. Host physiology and immune strategies are another factor that can influence epidemics. Two commonly examined strategies are tolerance and resistance. Tolerance is the …

Osteoimmunology And The Reconstruction Of Host Immunological Status In Treponemal Infection: Effect Of Activated Immune Cells By Oral Pathogens And Treponema Pallidum On Osteoclastogenesis., Michayla Gatsos

College of Arts & Sciences Senior Theses

Syphilitic infection caused by bacterium Treponema pallidum pallidum (Tp) offers an excellent model to study the long-lasting interplay between the immune and skeletal systems and could be used to reconstruct host immunological status. We propose that a hyper-inflammatory phenotype developed during acquired syphilis will have a systemic impact on most bone microenvironments involving inflammatory processes, such as the one developed in periodontal disease (PD). Using osteoimmunological in vitro protocols, we explore whether immune activation by Tp antigens and PD pathogens can impact osteoclastogenesis (OCG), ultimately helping to understand the bone alterations caused by systemic inflammatory processes in skeletal material. We …

Potency Of Novel Anti-Toxoplasmic Compounds, Matthias Walters

Theses/Capstones/Creative Projects

Toxoplasma gondii, the causative agent of toxoplasmosis, is an intracellular apicomplexan parasite. Toxoplasmosis is often asymptomatic, though, it can be debilitating or fatal to immunocompromised individuals and fetuses, being one of the leading causes of fetal mortality and birth defects. Toxoplasmosis is treated with a synergistic combination of drugs pyrimethamine and sulfadiazine; however, these drugs are only effective against the acute stage of infection, and the pyrimethamine is relatively cytotoxic, damaging bone marrow and causing noxious side effects. Due to these limitations, a safer alternative that targets the chronic stage of infection is needed. In this study, we tested …